Study phase:

During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

Site IRB:

Scottsdale/Phoenix, Arizona: 13-008752

Rochester, Minnesota: 13-008752

NCT ID:

NCT01886872

Sponsor Protocol Number:

A041202

About this study

This randomized phase III trial studies rituximab with bendamustine hydrochloride or ibrutinib to see how well they work compared to ibrutinib alone in treating older patients with previously untreated chronic lymphocytic leukemia. Monoclonal antibodies, such as rituximab, can block cancer growth in difference ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet know whether rituximab with bendamustine hydrochloride is more effective than rituximab and ibrutinib or ibrutinib alone in treating chronic lymphocytic leukemia.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

Patients must be diagnosed with CLL in accordance with International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria that includes all of the following:

≥ 5 x10^9 B lymphocytes (5000/uL) in the peripheral blood

On morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes

CLL cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5; patients with bright surface immunoglobulin expression or lack of CD23 expression in > 10% of cells must lack t(11;14) translocation by interphase cytogenetics

Patients must be intermediate or high-risk Rai stage CLL

Intermediate risk (formerly Rai stage I/II) is defined by lymphocytosis plus enlarged lymph nodes at any site, with or without hepatomegaly or splenomegaly

Fevers > 100.5 degrees F for 2 weeks or more without evidence of infection

Night sweats > 1 month without evidence of infection

Prior Treatment

Patients must not have had prior therapy for CLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids)

Treatment with rituximab and/or high dose corticosteroids for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment; palliative steroids must be at a dose not higher than 20 mg/day of prednisone or equivalent corticosteroid at the time of registration

Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Patients with active hepatitis B defined by hepatitis B surface antigen positivity or core antibody positivity in the presence of hepatitis B DNA are not eligible for this study; patients with a positive hepatitis B core antibody but with negative hepatitis B DNA may participate, but must have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician

Intravenous immunoglobulin (IVIG) can cause a false positive hepatitis B serology; if patients receiving routine IVIG have core antibody or surface antigen positivity without evidence of active viremia (negative hepatitis B DNA) they may still participate in the study, but should have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician

Patients must not be receiving active systemic anticoagulation with heparin or warfarin; patients must be off warfarin therapy for at least 30 days prior to enrollment

Patients with class III or class IV heart failure by New York Heart Association, those with unstable angina, and those with uncontrolled arrhythmia are not eligible

Patients who have had a myocardial infarction, intracranial bleed, or stroke within the past 6 months are not eligible

Patients with human immunodeficiency virus (HIV) are eligible if their CD4 count is ≥ 350 cells/mm^3 and if they are not taking prohibited cytochrome (CYP)-interacting medications

Patients must not have any history of Richter's transformation or prolymphocytic leukemia (prolymphocytes in blood > 55%)

Patients must not require more than 20 mg prednisone or equivalent corticosteroid daily

Patients must not have continued requirement for therapy with a strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitor or inducer

Patients must not have a known allergy to mannitol

Patients must not have prior significant hypersensitivity to rituximab (not including infusion reactions)

Patients may not have had major surgery within 10 days of enrollment, or minor surgery within 7 days of enrollment; examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint; the decision about whether a surgery is major or minor can be made at the discretion of the treating physician

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